The Emu as a Model for Necrotic Femoral Head Collapse

鸸鹋作为股骨头坏死模型

• 批准号: 6723786
• 负责人: THOMAS DUDLEY BROWN
• 金额: $ 41.11万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6723786
• 关键词: Aves; biomechanics; bone necrosis; computed axial tomography; disease /disorder model; dogs; femur; hip; magnetic resonance imaging; model design /development; orthopedics; osteocytes; pathologic process; skeletal stress

DESCRIPTION (provided by applicant): Femoral head osteonecrosis remains a major unsolved problem in orthopedic surgery of the hip. Because total hip replacement often proves unsatisfactory for patients with this disorder, means are needed to forestall necrotic femoral head collapse. Much could be learned from an animal model reliably mimicking the human disorder's natural history of structural collapse. Existing quadrupedal models fail to replicate this key aspect of the pathogenesis, presumably owing to unduly benign biomechanical demand. Cryogenically-induced osteonecrosis in the emu, a large and very active biped, shows great promise for overcoming this difficulty. The central goal of the proposed work is to bring this new emu model optimally into concordance with human disorder. Aim 1 is to establish quantitative linkage between cryo-insult parameters and resulting distributions of osteocyte death. This will involve thermal finite element analysis of temperature fields produced by a specially developed cryo-insult probe, and prediction of corresponding patterns of osteocyte death. Validation will be provided by osteocyte death distributions resulting from corresponding insults delivered intraoperatively. Aim 2 is to quantify the functional similarity of femoral head mechanical load transmission in emus versus humans. In vivo joint loading of the emu hip will be determined from force plate and optoelectronic recordings. Bench tests will be performed to measure hip joint contact stress distributions, and to map cancellous bone stiffness distributions. A whole-gait-cycle structural finite element model of the emu femoral head will be developed, for comparison with corresponding data for the human. Aim 3 is to compare the pathogenesis of osteonecrosis in emus with that in a (non-collapsing) canine model. Parameters of interest include the speed and patterns of revascularization, cell types, histomorphometric alterations of the trabecular lattice, and mechanical compromise. Aim 4 is to correlate the speed and severity of collapse in the emu osteonecrosis model with quantifiable structural compromise. This will again involve the structural finite element model, coupled with CT-based assessments of bony structural degradation. At the project's conclusion, we expect to have filled a longstanding need in the field of osteonecrosis research: an animal model suitable for systematic study of human-implementable interventions to forestall femoral head collapse.

描述（由申请人提供）：股骨头坏死仍然是髋关节矫形外科手术中尚未解决的主要问题。由于全髋关节置换术对于患有这种疾病的患者来说通常不能令人满意，因此需要采取措施来防止股骨头坏死塌陷。从可靠地模仿人类疾病结构崩溃的自然历史的动物模型中可以学到很多东西。现有的四足动物模型未能复制发病机制的这一关键方面，可能是由于生物力学需求过于良性。鸸鹋是一种大型且非常活跃的两足动物，低温引起的骨坏死显示出克服这一困难的巨大希望。拟议工作的中心目标是使这种新的鸸鹋模型与人类疾病保持最佳一致。目标 1 是建立冷冻损伤参数与骨细胞死亡分布之间的定量联系。这将涉及对专门开发的低温损伤探针产生的温度场进行热有限元分析，并预测相应的骨细胞死亡模式。将通过术中相应损伤引起的骨细胞死亡分布来提供验证。目标 2 是量化鸸鹋与人类股骨头机械负载传递的功能相似性。鸸鹋髋部的体内关节负荷将通过测力板和光电记录来确定。将进行台架测试来测量髋关节接触应力分布，并绘制松质骨硬度分布图。将开发鸸鹋股骨头的全步态周期结构有限元模型，以与人类的相应数据进行比较。目标 3 是比较鸸鹋和（非塌陷）犬科动物模型中骨坏死的发病机制。感兴趣的参数包括血运重建的速度和模式、细胞类型、小梁晶格的组织形态变化以及机械妥协。目标 4 是将鸸鹋骨坏死模型中塌陷的速度和严重程度与可量化的结构破坏相关联。这将再次涉及结构有限元模型，以及基于 CT 的骨结构退化评估。在该项目结束时，我们期望能够满足骨坏死研究领域的长期需求：一种适合系统研究人类可实施的预防股骨头塌陷干预措施的动物模型。